Mayra Lima

Endoscopic ultrasound restaging after neoadjuvant chemotherapy in esophageal cancer.

BACKGROUND:The role of endoscopic ultrasound (EUS) to evaluate treatment response postneoadjuvant therapy for restaging esophageal cancer prior to surgical resection is uncertain. Accuracy of EUS is lower but potential to predict response to chemoradiation indicates that EUS may be helpful prior to surgery.OBJECTIVE:To determine staging accuracy of EUS after neoadjuvant chemotherapy, predictors of tumor response, and survival in locally advanced esophageal cancer.METHODS:Single-center retrospective evaluation of patients with locally advanced esophageal cancer on a prospective chemotherapy study. Patients who underwent EUS without FNA pre- and postchemotherapy were included.RESULTS:A total of 49 patients (43 men and 6 women) were evaluated with EUS pre- and postneoadjuvant chemotherapy. Forty-seven patients had tumor localized at the GE junction and two had mid-esophageal lesions. The median survival time was 53 months. Tumor and nodal staging accuracy postchemotherapy were 60% (27 of 45). T-stage accuracy postchemotherapy was superior in patients without a response to chemotherapy (95.7% vs 26.1%, p < 0.0001). More than 50% in reduction of tumor thickness postchemotherapy was associated with tumor downstage and better survival. N0 disease on final pathology was the best predictor of improved survival.CONCLUSION:Accuracy of EUS postchemotherapy is lower than initial staging accuracy; therefore the ability to predict downstaging based on EUS is marginal. Pathology N1 disease postchemotherapy is the best predictor of survival. EUS staging postneoadjuvant chemotherapy should focus on improving nodal staging accuracy with FNA.

A Phase I Study of 5-Fluorouracil/Leucovorin and Arsenic Trioxide for Patients with Refractory/Relapsed Colorectal Carcinoma

Purpose: This Phase I study was designed to determine a safe combination dose of 5-fluorouracil (5-FU) and arsenic trioxide (ATO) to treat 5-FU–resistant relapsed/refractory colorectal cancer patients. We studied the effect of ATO in the downregulation of thymidylate synthase (TS) in peripheral blood mononuclear cells and in tumor biopsies. Experimental Design: ATO was administered for 5 consecutive days during the first week and twice during weeks 2 to 3 and once on week 4. 5-FU/leucovorin (LV) was administered on days 8, 15, and 22. A modified accelerated titration design was used. 5-FU was dose escalated first followed by a planned dose increase for ATO. Results: No dose-limiting toxicities were seen in seven patients who received 0.15 mg/kg ATO; grade 3 toxicities were as follows: neutropenia 1, diarrhea 1, and bowel obstruction 1. In patients receiving 0.20 mg/kg ATO, grade 3 toxicities were QTc prolongation 1, fatigue 4, alkaline phosphatase elevation 2, diarrhea 2, and peripheral edema 1. TS gene expression in peripheral blood mononuclear cell decreased in all patients. Eight tumors were biopsied, four showed TS downregulation, three showed upregulations, and one did not change. Estimated median progression-free survival and overall survival were 3.1 and 13.9 months, respectively. In patients who showed TS increase or no change versus TS reduction, estimated median progression-free survival was 2.6 versus 7.9 months (P = 0.188) and overall survival was 8.6 versus 11.7 months (P = 0.44), respectively. Conclusions: Thus, we determined 0.20 mg/kg ATO, 2,600 mg/m2 5-FU, and 500 mg/m2 leucovorin (LV) to be the recommended phase II dose. Clin Cancer Res; 16(11); 3019–27. ©2010 AACR.

Arsenic trioxide/ascorbic acid therapy in patients with refractory metastatic colorectal carcinoma: A clinical experience

Arsenic trioxide (As2O3) has demonstrated effectiveness in treating acute promyelocytic leukemia (APL). Therefore the FDA has approved it to treat APL. In patients with refractory metastatic colorectal carcinoma (CRC), we assessed the efficacy and toxicity of As2O3/AA (ascorbic acid) as the outcome of this trial. Five patients with refractory metastatic CRC who failed all previous standard chemotherapy were enrolled in this study. They were treated with 0.25 mg/kg body weight/day As2O3 and 1000 mg/day of ascorbic acid for 5 days a week for 5 weeks. Each treatment cycle extended for 7 weeks with 5 weeks of treatment and 2 weeks of rest. All the patients developed moderate to severe toxic side effects to arsenic trioxide/AA therapy and therefore the study was discontinued. No CR (complete remission) or PR (partial remission) was observed. CT scans demonstrated stable or progressive disease. Three of the five patients died within 2 to 5 months after cessation of the therapy. None of the deaths could be related to this clinical trial. Two years of follow-up study showed that two patients were alive with stable disease. Under the current treatment regimen all patients developed moderate to severe side effects with no clinically measurable activity. As an alternate, efforts may be made to reduce the dose and arsenic trioxide may be combined with other standard regimen in reversing the chemo resistance.

A phase II study of irinotecan, high-dose 24-h continuous intravenous infusion of floxuridine and leucovorin (IFLUX) for advanced, previously untreated colorectal cancer

Our objectives were to determine response rate, time to progression, overall survival and tolerability of novel combination chemotherapy, consisting of irinotecan, high-dose 24-h continuous intravenous infusion of floxuridine and leucovorin in advanced previously untreated colorectal cancer. Thirty-eight patients with advanced colorectal cancer were treated at Sylvester Comprehensive Cancer Center, University of Miami, from 2000 to 2004, and received weekly intravenous infusion of irinotecan at 110 mg/m2 with a combination of 120 mg/kg floxuridine and 500 mg/m2 leucovorin administered as a 24-h continuous intravenous infusion. The treatment cycle consisted of 4 weeks of consecutive therapy followed by 2 weeks of rest. Five (13%) patients achieved complete response, 10 (26%) patients achieved partial response, 17 (45%) patients attained stable disease and six (16%) patients progressed. The overall response rate was 39% in this study. This chemotherapy regiment was well tolerated; the most common grade 3 toxicities were neutropenia (16%), anemia (16%), vomiting (24%), diarrhea (16%), and hand-and-foot syndrome (26%). The median time to progression was 11.5 months (347.5 days) with 95% confidence intervals of 6.8–12.9 months (206–389 days). The time to progression ranged from 1.8 to 34 months. The median survival of the patients in this trial was 31.28 months (952 days) with a confidence interval of 20.9–38.0 months (629–1141 days). Intravenous infusion of floxuridine and leucovorin is beneficial as first-line therapy in advanced colorectal cancer, demonstrating a prolonged time to progression and overall survival with acceptable tolerability and manageable toxicity profile.

Abstract IA06: [Advocate Abstract:] A Tale of Two Cases

Breast Cancer is the most common type amongst women and the second leading cause of cancer deaths in the United States. We know from research that the relative 5 year survival rate for women diagnosed with early stage breast cancer is 98% compared to 23% for late stage. Disparities in cancer come in many shapes and forms and research has shown that they can affect outcomes. The three common types of disparities are: low socioeconomic status; cultural issues, and social biases. These are not exclusive of each other, and often appear in combination. In South Florida we are blessed with a diverse community with Hispanics, African Americans, Native Americans, and people of Caribbean background, creating a rich cultural ambience. These cultures and ethnicities have many common characteristics such as the love and support of family, beautiful music and delicious foods. Unfortunately, they also have a high incidence of low socioeconomic status, high incident of advanced cancer at diagnosis, and high mortality rate from a diagnosis of cancer. There are important lessons that can be learned from the rich and unique character of breast cancer care in South Florida. Citation Format: Mayra A. Lima. [Advocate Abstract:] A Tale of Two Cases. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr IA06.

Phase II neoadjuvant and adjuvant chemotherapy for localized esophageal carcinoma

4147 Background: Patients (Pts) with localized esophageal carcinoma were evaluated for toxicity, operative mortality/morbidity, and overall survivorship in a regimen that did NOT contain radiation therapy. METHODS Pts with T3N1M0 esophageal carcinoma confirmed by endoscopic ultrasound and CAT scan were eligible for this study. Our therapy consisted of combined Cisplatin100 mg/m2, Paclitaxel (Taxol) 125mg/ m2, Fluorodeoxyuridine (FUdR) 150 mg /Kg or 80 mg/Kg, and Leucovorin 500mg /m2. Chemotherapy was given for 16 weeks prior to surgery. Adjuvant chemotherapy was administered for the patients whose pathology at the time of the surgery demonstrated microscopic disease. RESULTS 33 pts (29 males, 4 females) with adenocarcinoma (n=30) or squamous cell carcinoma (n=3) were enrolled. 26 pts (78%) were symptomatic with dysphagia at the time of enrollment on the study. 28 pts completed two cycles of neoadjuvant chemotherapy, 19 (68%) showed improvement of dysphagia. There were 9 instances of grade 3 or 4 hematological toxicity. There were 11 instances of non-hematological grades 3-4 toxicities: fatigue (4), nausea (1) diarrhea (2) and stomatitis (4). Of 33 R0 resections, 5(15%) had no gross disease, 2 (6%) had no microscopic residual disease. Major surgical complication occurred in 5(15%) of 33 pts. Operative mortality was 1 of 33 pts. CONCLUSIONS Our regimen of preoperative and postoperative chemotherapy without radiation for esophageal carcinoma has produced a rapid relief of dysphagia, acceptable toxicity and durable response rates. No patient developed local recurrence, however, 14 pts developed distant metastasis, the sites included: 1 rectum and mediastinal lymph node, 2 brain, 2 liver and lung, 1 liver and spleen, 3 bone, 4 liver, lung, and brain, and 1 lung. Seventeen pts died after being followed for a median of 12 months (range 2 to 43 months), while 16 others remain alive with median follow up of 39 months (range 5 to 60 months). Median survival was estimated to be 42 months with a 95% lower confidence bound of 14 months. The Kaplan-Meier estimates of 1- and 3-year survival were 75% (95%CI: 60-90%) and 50% (95%CI: 32 to 68%). No significant financial relationships to disclose.